Generation of neuronal diversity through switching genes expression in neural stem cells

Developmental Cell February 2005

Hiromi Laboratory, Division of Developmental Genetics

seven-up controls switching of transcription factors that specify temporal identities of Drosophila neuroblasts
Kanai MI, Okabe M, Hiromi Y.
Developmental Cell, 8(2) 203-213, 2005

Drosophila neuronal stem cell neuroblasts (NB) constantly change character upon division, to produce a different type of progeny at the next division. Transcription factors Hunchback (HB), Kruppel (KR), Pdm (PDM), etc. are expressed sequentially in each NB and act as determinants of birth-order identity. How a NB switches its expression profile from one transcription factor to the next is poorly understood. We show that the HB-to-KR switch is directed by the nuclear receptor Seven-up (SVP). SVP expression is confined to a temporally restricted subsection within the NB's lineage. Loss of SVP function causes an increase in the number of HB-positive cells within several NB lineages, whereas misexpression of svp leads to the loss of these early-born neurons. Lineage analysis provides evidence that svp is required to switch off HB at the proper time. Thus, svp modifies the self-renewal stem cell program to allow chronological change of cell fates, thereby generating neuronal diversity.




Typical stem cell (left) produces only one kind of progeny through "self renewal" type of cell division. Neural stem cells (middle) generates a large variety of neuronal and glial cell types, by changing its expression pattern of transcription factors such as Hunchback (HB) and Kruppel (KR). Kanai et al. show that this HB-to-KR switch is controlled by Nuclear receptor Seven-up. In seven-up mutant (right), neuroblasts continue to produces the same kind of neurons, as if "reverting" to the self renewal type division.


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